Upper Respiratory Infections



Upper Respiratory Infections


Karleen Melody

Anisha B. Grover



Upper respiratory tract infections (URIs), including the common cold and rhinosinusitis, are some of the most common problems seen in primary care. URIs are usually self-limiting, minor illnesses that account for half or more of all acute illnesses. It is difficult to differentiate the common cold from rhinosinusitis or allergic rhinitis (see Chapter 48). URIs commonly involve rhinitis, which refers to irritation and inflammation of the intranasal mucous membrane and is characterized by nasal congestion, nasal discharge, sneezing, and postnasal drip. Other common URI symptoms include tenderness over the sinuses, fever, headache, malaise, sore throat, myalgias, a full feeling around the eyes and ears, and coughing. Symptoms may present individually or in combination, and it can be difficult to determine whether the cause is viral or bacterial.

URIs can progress to involve acute or chronic complications. In children especially, URIs may progress to otitis media. In a small percentage of cases, the viral or bacterial cause may travel, causing rhinosinusitis and bronchitis. Acute respiratory infections have been projected to kill approximately 3.9 million people annually and represent a leading cause of mortality in children living in developing countries who are less than 5 years of age (Liu et al., 2012). There also is an enormous economic burden associated with URIs.


COMMON COLD

Acute infectious rhinitis, also known as the common cold, nasopharyngitis, rhinopharyngitis, or acute coryza, is caused by one of more than 200 viral types and most commonly involves rhinovirus. It is one of the most common infections and is usually minor and self-limiting. Coryza is an acute inflammation of the mucous membranes of the respiratory passages, particularly of the nose, sinuses, and throat, and is characterized by sneezing, rhinorrhea (watery nasal discharge), and coughing.

In 2012, the U.S. Attitudes of Consumers Toward Health, Cough, and Cold (ACHOO) survey was developed to collect information regarding participant demographics, basic knowledge of cough and cold symptoms, treatment choices, and treatment preferences (Blaiss et al., 2015). Of the 2,505 survey participants, 84.6% had experienced at least one cold in the past year and lasted approximately 1 to 7 days. Cough was the most common cold symptom, affecting 73.1% of participants, and this symptom, along with nasal congestion, was reported as the most bothersome symptom. A subsequent publication examined the data from this study in order to assess the impact of cough and cold on daily activity, productivity, and absenteeism (Dicpinigaitis et al., 2015). Fifty-two percent of participants described the impact on daily life as a “fair amount” to “a lot” for the duration of the illness (Dicpinigaitis et al., 2015). During the time of a cold, participants reported a decrease in productivity by a mean of 26.4%. Almost half of respondents reported absenteeism from work or school lasting 1 to 2 days (Dicpinigaitis et al., 2015). A survey published in 2002 reported an approximate $2 billion spent in the United States annually on over-the-counter (OTC) preparations to relieve cold symptoms, predominantly in children (West, 2002). Another survey published in 2003 estimated that noninfluenza viral respiratory infections result in an annual $40 billion in costs. This includes costs related to cold-related absenteeism, including 70 million missed workdays, 186 million missed school days, and 126 million missed workdays among caregivers of children suffering from colds (Fendrick et al., 2003).



CAUSES

The pathogen most frequently associated with common colds is human rhinovirus (HRV), a single-stranded ribonucleic acid accounting for one half to two thirds of common colds (Jacobs et al., 2013). The coronavirus, respiratory syncytial virus, influenza virus, human parainfluenza virus, human metapneumovirus, and adenovirus can also contribute to cold-like symptoms, but HRVs are the single most pervasive cause of colds and in some cases can increase the susceptibility to bacterial infection within the upper and lower airway epithelial cells (Jacobs et al., 2013).

Predisposition to viral infections can be attributed to many factors, including frequent exposure to viral infectious agents; in children, the age of the child; and the inability to resist invading organisms because of allergies, malnutrition, immune deficiencies, physical abnormalities, or other comorbid conditions. Some experts propose a relationship between the host response to the virus and the production of cold symptoms. Studies show that common colds are more frequent or more severe in those under increased stress, probably as a result of stress weakening the immune system.



PATHOPHYSIOLOGY

If there is a breakdown or failure in the protective barriers of the URI (i.e., cough, gag, and sneeze reflexes, lymph nodes, immunoglobulin [Ig] A antibodies, and rich vasculature), viral pathogens trigger an acute inflammatory reaction with release of vasoactive mediators and increased parasympathetic stimuli. This produces congestion and rhinorrhea. Viral URI also produces inflammatory mediators that increase the sensitivity of afferent sensory nerves in the airway, which may contribute to the cough typically associated with the common cold.

Bradykinin and lysyl-bradykinin contribute to the pathogenesis of HRV infections. An increase in kinin levels is associated with increased permeability of the vasculature. However, histamine levels remain unchanged, indicating the lack of involvement of mast cells and basophils (Jacobs et al., 2013). The involvement of prostaglandins can be elucidated by the demonstrated effectiveness of cyclooxygenase inhibitors in reducing headache, malaise, myalgias, and cough during HRV infection.

Transmission of HRV occurs predominantly by intranasal or conjunctival inoculation and has been attributed to three methods: airborne transmission by small particles (droplets), airborne transmission by large particles, and direct contact. Large particle transmission is not efficient and requires prolonged exposure. Direct contact involves donor nose-to-hand contact, which is then transmitted to the hand of a recipient. From there, transmission occurs primarily when the infected hand makes contact with the eyes or nose. Although conjunctival cells are not thought to harbor HRV, it probably can be passed through the tear duct into the nose. HRVs can survive indoors for a range of hours to days at room temperature (Jacobs et al., 2013). Rhinoviruses grow in the upper airway and attach and gain entry to host cells by binding to an intracellular adhesion molecule. Infection begins in the adenoidal area and spreads to the ciliated epithelium in the nose. HRVs remain infectious for at least 3 hours after drying on hard surfaces such as telephones or countertops, but they do not last as long on porous surfaces, such as tissues.


DIAGNOSTIC CRITERIA

The expansion in the availability of laboratory diagnostics includes the collection and processing of specimens, detection and serology of antigens, conventional and rapid virus culture, and many other technologies; however, diagnostic tests are not recommended (Jacobs et al., 2013). In order to evaluate specimens, collection would have to occur as soon as possible after symptom onset, since HRV titers are most elevated during the first 2 days of clinical presentation. The short duration of most colds results in an impractical window of appropriate timing, and there are inaccuracies involved in the diagnostic process, making the testing process unreasonable.

The most commonly used method of diagnosis involves symptom evaluation. Onset of common cold signs and symptoms occurs 1 to 2 days after viral infection and peaks in approximately 2 to 4 days. A cough may persist following the resolution of other symptoms. Symptoms consist primarily of clear nasal discharge, sneezing, nasal congestion, cough, low-grade fever (below 102°F [38.9°C]), scratchy or sore throat, mild aches, chills, headache, watery eyes, tenderness around the eyes, full feeling in the ears, and fatigue. In children, the presentation could also include fever with seizures, anorexia, vomiting, diarrhea, and abdominal pain. Symptoms usually resolve in approximately 1 week, but they may linger for up to 2 weeks.


INITIATING DRUG THERAPY

Improper treatment of the common cold by clinicians is common for several reasons. It is often difficult to determine whether the cause is viral or bacterial. There is no cure for the common cold; therefore, treatment strategies are supportive in nature and consist primarily of symptom relief.

Nonpharmacologic alternatives to treating the common cold are the first line of treatment. Rest allows the body to gain strength. An alternative to decongestants and expectorants involves increasing water or juice intake, which assists in liquefying tenacious secretions, making expectoration easier, soothing scratchy, sore throats, and relieving dry skin and lips. Saline gargles also are effective for soothing sore throats. Saline nasal flushes and irrigation may have slight benefit in clearing nasal passages without the risk for rebound congestion; however, evidence remains limited (Fokkens et al., 2012).

Coughing caused by chest congestion can cause a muscular chest pain. Menthol rubs can soothe this ache and open
airways for some congestion relief. Menthol lozenges also have been effective in soothing scratchy throats and clearing nasal passages. Petrolatum-based ointments for raw and macerated skin around the nose and upper lip ease the drying effects of dehydration and the use of multiple tissues. Inhalation of steam has not demonstrated benefit in the drainage of mucus or the destruction of the cold virus and is therefore not recommended (Fokkens et al., 2012).


Goals of Drug Therapy

The main goals of treatment for the common cold are relief of symptoms, reduction of the risk for complications, and prevention of spread to others.


Decongestants

Decongestants come in topical or oral preparations and can be somewhat effective for the short-term relief of cold symptoms (Fashner et al., 2012). Topical decongestants, such as oxymetazoline hydrochloride (Afrin) and phenylephrine hydrochloride (Afrin Childrens, Little Remedies, Neo-synephrine), are available in nasal spray and pump mist preparations. Oral decongestants, such as pseudoephedrine (Sudafed) and phenylephrine (Sudafed PE), are also available. Decongestants are typically available OTC. Preparations containing pseudoephedrine can be obtained without a prescription but are available behind the counter and must be purchased from a pharmacy.


Mechanism of Action

Decongestants are sympathomimetic agents that stimulate alpha- and beta-adrenergic receptors, causing vasoconstriction in the respiratory tract mucosa and thereby improving ventilation. Topical decongestants have little systemic absorption but work locally by slowing ciliary motility and mucociliary clearance. Oral agents have the same mechanism of action and assist in the clearance of nasal mucus and obstruction. Their use may help to prevent rhinosinusitis and eustachian tube blockage in patients susceptible to these conditions.


Dosage

Oxymetazoline hydrochloride 0.05% nasal spray and pump mists can be used in patients who are at least 6 years old at a dosage of 2 to 3 sprays in each nostril not more often than every 10 to 12 hours. Patients should not exceed 2 doses of oxymetazoline in a 24-hour time period. Phenylephrine nasal sprays are available as 0.125%, 0.25%, 0.5%, and 1% preparations. For specific dosing recommendations, please see Table 24.1. Despite the ability to use the spray every 4 hours, it should generally not be used more than two to three times daily. Topical decongestants should not be used for more than 3 days because prolonged use can cause rhinitis medicamentosa (rebound congestion), which is characterized by severe nasal edema, rebound congestion, and increased discharge due to decreased receptor sensitivity. Rebound congestion interferes with ciliary action and dries the nasal mucosa.










TABLE 24.1 Overview of Agents for Upper Respiratory Infections














































































































































































































































































Generic (Trade) Name and Dosage

Selected Adverse Events

Contraindications

Special Considerations


Decongestants


oxymetazoline hydrochloride (Afrin, Mucinex Sinus, Neo-Synephrine, Vicks Sinex)

Palpitations, headaches

Hypersensitivity

These drugs may cause rebound congestion.


Use only 2-3 d, then switch to oral decongestants.

Nasal spray and pump mists (0.05%)


≥6 y: 2-3 sprays per nostril q10-12h


phenylephrine hydrochloride (Neo-Synephrine, Sudafed PE, Afrin Childrens)

Palpitations, headaches

Hypersensitivity, urinary retention, severe uncontrolled hypertension, coronary artery disease, MAO inhibitor use within 14 d

These drugs may cause rebound congestion.


Use only 2-3 d, then switch to oral decongestants.

Nasal spray (0.125%)


2-5 y: 2-3 sprays per nostril q4h

Mild nasal spray (0.25%)


6-12 y: 2-3 sprays per nostril q4h

Regular nasal spray (0.5%)


≥12 y: 2-3 sprays per nostril q4h

Extra strength nasal spray (1%)


≥12 y: 2-3 sprays per nostril q4h

Tablet, oral (10 mg)


≥12 y: 10 mg q4h


pseudoephedrine (Sudafed)

Palpitations, headaches, increased blood pressure, dizziness, GI upset, tremor, insomnia

Hypersensitivity, narrow-angle glaucoma, severe uncontrolled hypertension, coronary artery disease, MAO inhibitor use within 14 d

Give at least 2 h before bedtime. Do not crush, break, or chew tablets.

IR tablet, oral (30 mg)


≥12 y: 60 mg q4-6h


6-11 y: 30 mg q4-6h

12-hour tablet, oral (120 mg)


≥12 y: 120 mg q12h

ER tablet, oral (240 mg)


≥12 y: 240 mg q24h


Expectorants


guaifenesin (Antitussin, Mucinex, Robitussin, Uni-Tussin)

Drowsiness, headache, dizziness, GI upset

Hypersensitivity

Not given for prolonged time if cough persists or accompanied by high fever


Oral packet may be swallowed whole or opened and sprinkled on soft food.

Liquid, oral (100-200 mg/5 mL)


Solution, oral (100 mg/5 mL)


Syrup, oral (100 mg/5 mL)


Packet, oral (50 mg, 100 mg)


6 mo-12 y: 25-50 mg q4h


2-5 y: 50-100 mg q4h


6-12 y: 100-200 mg q4h


≥12 y: 200-400 mg q4h

IR tablet, oral (200 or 400 mg)


≥12 y: 200-400 mg q4h

ER tablet, oral (600 mg)


≥12 y: 600-1,200 mg q12h


Antitussives


dextromethorphan (Delsym)

Dizziness, nausea, drowsiness

Hypersensitivity, MAO inhibitor use within 14 d

None

Lozenge, oral (5 mg)


Capsule, oral, 15 mg


Sublingual strip, oral (7.5 mg)


Gel, oral (7.5 mg/5 mL)


Syrup, oral (varying strengths)


IR liquid, oral (varying strengths)


4-6 y: 2.5-7.5 mg q4-8h


6-12 y: 5-10 mg q4h


≥12 y: 10-20 mg q4h or 30 mg q6-8h

ER liquid, oral (30 mg/5 mL)


4-6 y: 15 mg q12h


6-12 y: 15 mg q6-8h


≥12 y: 60 mg q12h


benzonatate (Tessalon Perles)

Constipation, drowsiness, headache, GI upset, confusion

Hypersensitivity

Capsule, oral (100 or 200 mg)


≥10 y: 100-200 mg q8h


Anti-inflammatories


naproxen sodium (Naprosyn, Aleve)

Dizziness, drowsiness, headache, edema, abdominal pain, constipation, nausea, heartburn

Hypersensitivity

Take on full stomach to reduce GI upset.

Tablet, oral (220 mg)


≥12 y: 220 mg q8-12h


Anticholinergics


ipratropium bromide (Atrovent)

Headache, epistaxis, pharyngitis, nasal dryness

Hypersensitivity to atropine


Use caution in patients with narrow-angle glaucoma, BPH, bladder neck obstruction, pregnancy, and lactation

Safety and efficacy not established beyond 4 d

Nasal spray (0.06%)


≥12 y: 2 sprays per nostril bid-qid


5-11 y: 2 sprays per nostril tid


Antihistamines


diphenhydramine (Benadryl)

Confusion, dizziness, drowsiness, fatigue, paradoxical excitability, nervousness, headache, sedation, blurred vision, dry mouth, hallucinations, tachycardia, urinary retention

Hypersensitivity, patients who are breast-feeding, neonates, premature infants

Caution in elderly, as it may increase fall risk.

Tablet, oral (25 mg)


≥12 y: 25-50 mg q4-6h


chlorpheniramine (Chlor-Trimeton)

Headache, fatigue, nervousness, dizziness, nausea, dry mouth, GI upset, urinary retention, blurred vision

Hypersensitivity, narrow-angle glaucoma, bladder neck obstruction, symptomatic prostate hypertrophy, during acute asthma attacks, stenosing peptic ulcer, pyloroduodenal obstruction

Caution in elderly, as it may increase fall risk.

IR tablet, oral (4 mg)


≥12 y: 4 mg q4-6h

ER tablet, oral (12 mg)


≥12 y: 12 mg q12h


amoxicillin with clavulanic acid (Augmentin)

Common: GI upset, rash, vaginal infections, photosensitivity


Rare: Stevens-Johnson syndrome, seizures

Hypersensitivity or allergy to penicillin or cephalosporins


Do not use ER formulation in patients with CrCl < 30 mL/min

“High dose” (2 g q12h) is reserved for patients with risk for antibiotic resistance.*

Adults or children >40 kg: 500 mg q8h


Children 3 mo to adolescence who are ≤40 kg: 20 mg/kg/d q8h or 25 mg/kg/d q12h


Children <3 mo: 30 mg/kg/d every 12 h


Children with severe ABRS: 40 mg/kg/d q8h or 45 mg/kg/d q12h


CrCl 10-30 mL/min: 250-500 mg q12h


CrCl < 10 mL/min: 250-500 mg q24h


Doxycycline (Oracea)

Common: GI upset, rash, vaginal infections, headache


Rare: Stevens-Johnson syndrome, hepatotoxicity

Hypersensitivity or allergy to tetracyclines

Not recommended for children ≤8 y of age


Take on an empty stomach if tolerated.

Adults and children >8 y of age weighing >45 kg: 200 mg daily in 1-2 divided doses


levofloxacin (Levaquin)

Common: GI upset, rash, dyspepsia, headache, chest pain, decreased blood glucose, edema, photosensitivity, vaginal infections


Black box warning for tendon inflammation and rupture

Hypersensitivity or allergy to fluoroquinolones

Avoid in patients with myasthenia gravis.


Can prolong QTc interval. Avoid concurrent use with other medications that prolong the QTc interval.


Avoid taking with corticosteroids due to increased risk of ruptured Achilles tendon.

Adults: 500-750 mg q24h


Children: 10-20 mg/kg/d q12-24h


CrCl 20-49 mL/min: 500 mg × 1 followed by 250 mg q24h or 500 mg × 1 followed by 750 mg q48h


moxifloxacin (Avelox)

Same as above

Same as above

Same as above

Adults: 400 mg q24h


clindamycin (Cleocin)

Common: GI upset

Hypersensitivity or allergy to lincosamides

Must be taken with third-generation cephalosporins.

Children: 30-40 mg/kg/d divided q8h


cefpodoxime (Vantin)

Common: GI upset headache

Caution with penicillin allergy

Interacts with antacids, H2 antagonists.

Children >2 mo and <12 y: 5 mg/kg q12h


Children ≥12 y: 200 mg q12h


cefixime (Suprax)

Same as above

Same as above

Same as above.

Children >6 mo and <12 y: 4 mg/kg q12h


Children ≥12 y: 400 mg divided every 12-24 h




* Patients with ABRS from regions with high endemic rates of resistant S. pneumoniae, those with severe infection, children in daycare, ages <2 or >65, immunosuppressed or those with a recent hospitalization or antibiotic use within the past month.



Oral pseudoephedrine is available in 30-mg tablets in preparations that vary with regard to duration of action. Adults greater than 12 years of age can take a short-acting preparation at a dose of 60 mg every 4 to 6 hours or a long-acting preparation at a dose of 120 mg every 12 hours. All-day preparations are also available at a dosage of 240 mg and should not be taken more than once in a 24-hour time period. Children who are 4 to 5 years of age can take a 15-mg dose every 4 to 6 hours to a maximum daily dose of 60 mg. Children aged 6 to 12 should take 30 mg every 4 to 6 hours and should not exceed 120 mg within 24 hours. Oral preparations should be given at least 2 hours before bedtime, and extended-release (ER) formulations should not be crushed, broken, or chewed. Oral phenylephrine has not demonstrated consistent benefit and should not be recommended.


Time Frame for Response

Topical decongestants have a rapid onset of action and can begin to work within several minutes. Oral decongestants have a slower onset of action of approximately 30 minutes.



Contraindications

Decongestants are contraindicated in patients with hypersensitivity to any component of the formulation, narrow-angle glaucoma, severe uncontrolled hypertension, and coronary artery disease and in patients who have been treated with a monoamine oxidase (MAO) inhibitor within 14 days. Caution is recommended in patients with hypertension, cardiovascular disease, renal impairment, hyperthyroidism, diabetes, prostatic hypertrophy, and urinary incontinence.


Adverse Events

Adverse drug events (ADEs) include increased blood pressure and heart rate, palpitations, headache, dizziness, gastrointestinal (GI) distress, insomnia, and tremor. These reactions are especially seen at doses above 210 mg. In patients with controlled hypertension, products can be taken for a short course and with frequent monitoring.


Interactions

Decongestants interact with appetite suppressants, MAO inhibitors (hypertensive crisis), and beta-adrenergic agents (bradycardia and hypertension). Decongestants are less effective when taken with drugs that acidify the urine and more effective when taken with drugs that alkalize the urine.


Expectorants

One of the most important nondrug considerations in treating coughs involves an exploration of the etiology, because the prolonged use of OTC expectorants or other cough products may mask symptoms of a serious underlying disorder. This drug should not be used for more than 1 week. If the cough persists, additional measures should be investigated. The most commonly available expectorant is guaifenesin (Antitussin, Mucinex, Robitussin). Some studies have shown this product to have limited advantage over increased fluid intake, and evidence regarding benefit is generally controversial (Fashner et al., 2012).


Mechanism of Action

Expectorants, including water, increase the output of respiratory tract fluid by decreasing the adhesiveness and surface tension of the respiratory tract and by facilitating the removal of viscous mucous.


Dosage

Guaifenesin is available in both liquid and tablet oral preparations. Some preparations are available in the form of oral sprinkles, which may be swallowed whole or sprinkled on soft food, such as applesauce. The recommended dose for adults over the age of 12 is 200 to 400 mg every 4 hours to a maximum daily dose of 2.4 grams (g). ER tablets can be taken at a dosage of 600 to 1,200 mg every 12 hours, with the same maximum daily dose as the immediate-release (IR) preparations. For children less than 4 years of age, a physician or pharmacist should be consulted prior to treatment with expectorants. If recommended by a health care professional, children aged 6 months to 2 years can be given a dose of 25 to 50 mg every 4 hours to a maximum of 300 mg/d. Children aged 2 to 5 can take a dose of 50 to 100 mg every 4 hours, not to exceed 500 mg/d. Children who are 6 to 12 years of age can be given a dose of 100 to 200 mg every 4 hours to a maximum of 1.2 mg/d.


Time Frame for Response

Expectorants have an onset of action of approximately 1 to 2 hours.



Contraindications

Expectorants are contraindicated in patients with hypersensitivity to any component of the formulation.


Adverse Events

ADEs include drowsiness, headache, dizziness, and GI upset.


Interactions

There are no known drug interactions.


Antitussives

Cough suppressants, such as dextromethorphan (Delsym) and benzonatate (Tessalon Perles), are available in oral preparations, including liquids, gels, capsules, lozenges, and sublingual strips, but studies have shown minimal benefit with the common cold (Fashner et al., 2012). For some patients, these agents may reduce cough frequency and help achieve sleep; however, consistent benefit has not been demonstrated. There is little evidence to support the use of narcotic antitussives, such as codeine and hydrocodone, to relieve cough. Many practitioners believe that cough suppressants are ineffective in children.

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Nov 11, 2018 | Posted by in PHARMACY | Comments Off on Upper Respiratory Infections

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